Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1985 Aug;4(8):1945–1949. doi: 10.1002/j.1460-2075.1985.tb03875.x

Highly purified fibroblast-derived growth factor, an SV40-transformed fibroblast-secreted mitogen, is closely related to platelet-derived growth factor.

P Stroobant, W J Gullick, M D Waterfield, E Rozengurt
PMCID: PMC554445  PMID: 2998776

Abstract

Fibroblast-derived growth factor (FDGF), a polypeptide secreted by an SV40-transformed baby hamster kidney cell line (SV28), was purified approximately 1000-fold from SV28-conditioned medium. FDGF, which gave a single band on SDS-polyacrylamide gel electrophoresis, is a hydrophobic and cationic protein of apparent mol. wt. 31 000 containing disulphide-linked polypeptides. This factor is positive in Western blots using human platelet-derived growth factor (PDGF) anti-serum. FDGF is a potent mitogen for Swiss 3T3 cells; half-maximal stimulation of DNA synthesis was achieved at a concentration of approximately 1 nM, comparable with those for human and porcine PDGF. FDGF inhibits EGF binding to Swiss 3T3 cells, as does PDGF. The coincidence of the physical, biological and immunological characteristics of FDGF and PDGF strongly suggests that they are closely related in structure.

Full text

PDF
1945

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anzano M. A., Roberts A. B., Meyers C. A., Komoriya A., Lamb L. C., Smith J. M., Sporn M. B. Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells. Cancer Res. 1982 Nov;42(11):4776–4778. [PubMed] [Google Scholar]
  2. Betsholtz C., Heldin C. H., Nister M., Ek B., Wasteson A., Westermark B. Synthesis of a PDGF-like growth factor in human glioma and sarcoma cells suggests the expression of the cellular homologue to the transforming protein of simian sarcoma virus. Biochem Biophys Res Commun. 1983 Nov 30;117(1):176–182. doi: 10.1016/0006-291x(83)91557-7. [DOI] [PubMed] [Google Scholar]
  3. Bourne H. R., Rozengurt E. An 18,000 molecular weight polypeptide induces early events and stimulates DNA synthesis in cultured cells. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4555–4559. doi: 10.1073/pnas.73.12.4555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bowen-Pope D. F., Dicorleto P. E., Ross R. Interactions between the receptors for platelet-derived growth factor and epidermal growth factor. J Cell Biol. 1983 Mar;96(3):679–683. doi: 10.1083/jcb.96.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bowen-Pope D. F., Vogel A., Ross R. Production of platelet-derived growth factor-like molecules and reduced expression of platelet-derived growth factor receptors accompany transformation by a wide spectrum of agents. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2396–2400. doi: 10.1073/pnas.81.8.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  7. Chiu I. M., Reddy E. P., Givol D., Robbins K. C., Tronick S. R., Aaronson S. A. Nucleotide sequence analysis identifies the human c-sis proto-oncogene as a structural gene for platelet-derived growth factor. Cell. 1984 May;37(1):123–129. doi: 10.1016/0092-8674(84)90307-6. [DOI] [PubMed] [Google Scholar]
  8. Collins M. K., Sinnett-Smith J. W., Rozengurt E. Platelet-derived growth factor treatment decreases the affinity of the epidermal growth factor receptors of Swiss 3T3 cells. J Biol Chem. 1983 Oct 10;258(19):11689–11693. [PubMed] [Google Scholar]
  9. De Larco J. E., Tadaro G. J. A human fibrosarcoma cell line producing multiplication stimulating activity (MSA)-related peptides. Nature. 1978 Mar 23;272(5651):356–358. doi: 10.1038/272356a0. [DOI] [PubMed] [Google Scholar]
  10. Deuel T. F., Huang J. S., Huang S. S., Stroobant P., Waterfield M. D. Expression of a platelet-derived growth factor-like protein in simian sarcoma virus transformed cells. Science. 1983 Sep 30;221(4618):1348–1350. doi: 10.1126/science.6310754. [DOI] [PubMed] [Google Scholar]
  11. Deuel T. F., Huang J. S. Platelet-derived growth factor: purification, properties, and biological activities. Prog Hematol. 1983;13:201–221. [PubMed] [Google Scholar]
  12. DiCorleto P. E. Cultured endothelial cells produce multiple growth factors for connective tissue cells. Exp Cell Res. 1984 Jul;153(1):167–172. doi: 10.1016/0014-4827(84)90458-0. [DOI] [PubMed] [Google Scholar]
  13. Dicker P., Pohjanpelto P., Pettican P., Rozengurt E. Similarities between fibroblast-derived growth factor and platelet-derived growth factor. Exp Cell Res. 1981 Sep;135(1):221–227. doi: 10.1016/0014-4827(81)90314-1. [DOI] [PubMed] [Google Scholar]
  14. Dicker P., Rozengurt E. Phorbol esters and vasopressin stimulate DNA synthesis by a common mechanism. Nature. 1980 Oct 16;287(5783):607–612. doi: 10.1038/287607a0. [DOI] [PubMed] [Google Scholar]
  15. Dicker P., Rozengurt E. Stimulation of DNA synthesis by tumour promoter and pure mitogenic factors. Nature. 1978 Dec 14;276(5689):723–726. doi: 10.1038/276723a0. [DOI] [PubMed] [Google Scholar]
  16. Dicker P., Rozengurt E. Synergistic stimulation of early events and DNA synthesis by phorbol esters, polypeptide growth factors, and retinoids in cultured fibroblasts. J Supramol Struct. 1979;11(1):79–93. doi: 10.1002/jss.400110109. [DOI] [PubMed] [Google Scholar]
  17. Doolittle R. F., Hunkapiller M. W., Hood L. E., Devare S. G., Robbins K. C., Aaronson S. A., Antoniades H. N. Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983 Jul 15;221(4607):275–277. doi: 10.1126/science.6304883. [DOI] [PubMed] [Google Scholar]
  18. Dulak N. C., Temin H. M. Multiplication-stimulating activity for chicken embryo fibroblasts from rat liver cell conditioned medium: a family of small polypeptides. J Cell Physiol. 1973 Apr;81(2):161–170. doi: 10.1002/jcp.1040810205. [DOI] [PubMed] [Google Scholar]
  19. Eva A., Robbins K. C., Andersen P. R., Srinivasan A., Tronick S. R., Reddy E. P., Ellmore N. W., Galen A. T., Lautenberger J. A., Papas T. S. Cellular genes analogous to retroviral onc genes are transcribed in human tumour cells. Nature. 1982 Jan 14;295(5845):116–119. doi: 10.1038/295116a0. [DOI] [PubMed] [Google Scholar]
  20. Friedkin M., Legg A., Rozengurt E. Antitubulin agents enhance the stimulation of DNA synthesis by polypeptide growth factors in 3T3 mouse fibroblasts. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3909–3912. doi: 10.1073/pnas.76.8.3909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gazit A., Igarashi H., Chiu I. M., Srinivasan A., Yaniv A., Tronick S. R., Robbins K. C., Aaronson S. A. Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation. Cell. 1984 Nov;39(1):89–97. doi: 10.1016/0092-8674(84)90194-6. [DOI] [PubMed] [Google Scholar]
  22. Heldin C. H., Westermark B., Wasteson A. Chemical and biological properties of a growth factor from human-cultured osteosarcoma cells: resemblance with platelet-derived growth factor. J Cell Physiol. 1980 Nov;105(2):235–246. doi: 10.1002/jcp.1041050207. [DOI] [PubMed] [Google Scholar]
  23. Johnsson A., Heldin C. H., Wasteson A., Westermark B., Deuel T. F., Huang J. S., Seeburg P. H., Gray A., Ullrich A., Scrace G. The c-sis gene encodes a precursor of the B chain of platelet-derived growth factor. EMBO J. 1984 May;3(5):921–928. doi: 10.1002/j.1460-2075.1984.tb01908.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Josephs S. F., Guo C., Ratner L., Wong-Staal F. Human-proto-oncogene nucleotide sequences corresponding to the transforming region of simian sarcoma virus. Science. 1984 Feb 3;223(4635):487–491. doi: 10.1126/science.6318322. [DOI] [PubMed] [Google Scholar]
  25. Kaplan P. L., Ozanne B. Cellular responsiveness to growth factors correlates with a cell's ability to express the transformed phenotype. Cell. 1983 Jul;33(3):931–938. doi: 10.1016/0092-8674(83)90036-3. [DOI] [PubMed] [Google Scholar]
  26. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  27. Lopez-Rivas A., Stroobant P., Waterfield M. D., Rozengurt E. Ionic responses rapidly elicited by porcine platelet-derived growth factor in Swiss 3T3 cells. EMBO J. 1984 May;3(5):939–944. doi: 10.1002/j.1460-2075.1984.tb01911.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Niman H. L. Antisera to a synthetic peptide of the sis viral oncogene product recognize human platelet-derived growth factor. Nature. 1984 Jan 12;307(5947):180–183. doi: 10.1038/307180a0. [DOI] [PubMed] [Google Scholar]
  29. Niman H. L., Houghten R. A., Bowen-Pope D. F. Detection of high molecular weight forms of platelet-derived growth factor by sequence-specific antisera. Science. 1984 Nov 9;226(4675):701–703. doi: 10.1126/science.6494905. [DOI] [PubMed] [Google Scholar]
  30. Nistér M., Heldin C. H., Wasteson A., Westermark B. A glioma-derived analog to platelet-derived growth factor: demonstration of receptor competing activity and immunological crossreactivity. Proc Natl Acad Sci U S A. 1984 Feb;81(3):926–930. doi: 10.1073/pnas.81.3.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nistér M., Heldin C. H., Wasteson A., Westermark B. A platelet-derived growth factor analog produced by a human clonal glioma cell line. Ann N Y Acad Sci. 1982 Dec 10;397:25–33. doi: 10.1111/j.1749-6632.1982.tb43414.x. [DOI] [PubMed] [Google Scholar]
  32. Owen A. J., Pantazis P., Antoniades H. N. Simian sarcoma virus--transformed cells secrete a mitogen identical to platelet-derived growth factor. Science. 1984 Jul 6;225(4657):54–56. doi: 10.1126/science.6328659. [DOI] [PubMed] [Google Scholar]
  33. Robbins K. C., Antoniades H. N., Devare S. G., Hunkapiller M. W., Aaronson S. A. Structural and immunological similarities between simian sarcoma virus gene product(s) and human platelet-derived growth factor. Nature. 1983 Oct 13;305(5935):605–608. doi: 10.1038/305605a0. [DOI] [PubMed] [Google Scholar]
  34. Robbins K. C., Hill R. L., Aaronson S. A. Primate origin of the cell-derived sequences of simian sarcoma virus. J Virol. 1982 Feb;41(2):721–725. doi: 10.1128/jvi.41.2.721-725.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rozengurt E., Collins M., Brown K. D., Pettican P. Inhibition of epidermal growth factor binding to mouse cultured cells by fibroblast-derived growth factor. Evidence for an indirect mechanism. J Biol Chem. 1982 Apr 10;257(7):3680–3686. [PubMed] [Google Scholar]
  36. Rozengurt E., Heppel L. A. Serum rapidly stimulates ouabain-sensitive 86-RB+ influx in quiescent 3T3 cells. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4492–4495. doi: 10.1073/pnas.72.11.4492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rozengurt E., Legg A., Pettican P. Vasopressin stimulation of mouse 3T3 cell growth. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1284–1287. doi: 10.1073/pnas.76.3.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rozengurt E., Stroobant P., Waterfield M. D., Deuel T. F., Keehan M. Platelet-derived growth factor elicits cyclic AMP accumulation in Swiss 3T3 cells: role of prostaglandin production. Cell. 1983 Aug;34(1):265–272. doi: 10.1016/0092-8674(83)90157-5. [DOI] [PubMed] [Google Scholar]
  39. Seed B. Diazotizable arylamine cellulose papers for the coupling and hybridization of nucleic acids. Nucleic Acids Res. 1982 Mar 11;10(5):1799–1810. doi: 10.1093/nar/10.5.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Seifert R. A., Schwartz S. M., Bowen-Pope D. F. Developmentally regulated production of platelet-derived growth factor-like molecules. Nature. 1984 Oct 18;311(5987):669–671. doi: 10.1038/311669a0. [DOI] [PubMed] [Google Scholar]
  41. Slamon D. J., deKernion J. B., Verma I. M., Cline M. J. Expression of cellular oncogenes in human malignancies. Science. 1984 Apr 20;224(4646):256–262. doi: 10.1126/science.6538699. [DOI] [PubMed] [Google Scholar]
  42. Stroobant P., Waterfield M. D. Purification and properties of porcine platelet-derived growth factor. EMBO J. 1984 Dec 1;3(12):2963–2967. doi: 10.1002/j.1460-2075.1984.tb02241.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Symington J., Green M., Brackmann K. Immunoautoradiographic detection of proteins after electrophoretic transfer from gels to diazo-paper: analysis of adenovirus encoded proteins. Proc Natl Acad Sci U S A. 1981 Jan;78(1):177–181. doi: 10.1073/pnas.78.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. TODARO G. J., GREEN H. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol. 1963 May;17:299–313. doi: 10.1083/jcb.17.2.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Thiel H. J., Hafenrichter R. Simian sarcoma virus transformation-specific glycopeptide: immunological relationship to human platelet-derived growth factor. Virology. 1984 Jul 30;136(2):414–424. doi: 10.1016/0042-6822(84)90177-6. [DOI] [PubMed] [Google Scholar]
  46. Waterfield M. D., Scrace G. T., Whittle N., Stroobant P., Johnsson A., Wasteson A., Westermark B., Heldin C. H., Huang J. S., Deuel T. F. Platelet-derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus. Nature. 1983 Jul 7;304(5921):35–39. doi: 10.1038/304035a0. [DOI] [PubMed] [Google Scholar]
  47. Westermark B., Wasteson A. The response of cultured human normal glial cells to growth factors. Adv Metab Disord. 1975;8:85–100. doi: 10.1016/b978-0-12-027308-9.50012-3. [DOI] [PubMed] [Google Scholar]
  48. Westin E. H., Wong-Staal F., Gelmann E. P., Dalla-Favera R., Papas T. S., Lautenberger J. A., Eva A., Reddy E. P., Tronick S. R., Aaronson S. A. Expression of cellular homologues of retroviral onc genes in human hematopoietic cells. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2490–2494. doi: 10.1073/pnas.79.8.2490. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES